Design, synthesis of 8-alkoxy-5,6-dihydro-[1,2,4]triazino[4,3-a]quinolin-1-ones with anticonvulsant activity.
A new series of 8-alkoxy-5,6-dihydro-[1,2,4]triazino[4,3-a]quinolin-1-one derivatives were synthesized. Their anticonvulsant activities were evaluated by the maximal electroshock (MES) test, and their neurotoxicities were evaluated by the rotarod neurotoxicity test. The results showed that 8-heptyloxy-5,6-dihydro-[1,2,4]triazino[4,3-a]quinolin-1-one 5t was the most potent with median effective dose (ED(50)) value of 11.4 mg/kg, median toxicity dose (TD(50)) of 114.1 mg/kg, providing a protective index (PI=TD(50)/ED(50)) value of 10.0, which is much greater than the PI of the prototype drug carbamazepine (PI=6.4). To explain the possible mechanism of anticonvulsant activity, the compound 5t was tested in chemically induced seizures.
Sun
Xian-Yu
XY
Key Laboratory of Organism Functional Factors of the Changbai Mountain, Yanbian University, Ministry of Education, Yanji, Jilin 133002, China.
Zhang
Lei
L
Wei
Cheng-Xi
CX
Piao
Hu-Ri
HR
Quan
Zhe-Shan
ZS
D000927:Anticonvulsants / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D015195:Drug Design; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015363:Quinolones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D013055:Spectrophotometry, Infrared
D000927:Anticonvulsants; D015363:Quinolones